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Vs. Vehicle (vs + vehicle)
Selected AbstractsAssessment of the effect of 2-chloroadenosine in normal rat brain using spin-labeled MRI measurement of perfusionMAGNETIC RESONANCE IN MEDICINE, Issue 5 2001Patrick M. Kochanek Abstract Adenosine analogs such as 2-chloroadenosine are potent cerebrovasodilators. Spin-labeled MRI was used to investigate the spatial distribution, dose-response, and timing of the effect of 2-chloroadenosine on cerebral blood flow (CBF) after intraparenchymal injection into rat brain. Sprague-Dawley rats (N = 10) were injected with 2-chloroadenosine at doses of 0.3, 6.0, or 12 nmoles, or saline vehicle (2,4 ,L). CBF was serially quantified in a slice through the injection site in a circular (3.6 mm diameter) region of interest (ROI) around the injection and in ipsilateral hemispheric ROIs at ,90 min and ,180 min. Marked 3.77- and 3.93-fold increases in CBF (vs. vehicle) were seen in the circular ROI at ,90 min and ,180 min after 12-nmol injection, respectively. Similarly, 2.92- and 2.78-fold increases in hemispheric CBF were observed at ,90 min and ,180 min, respectively, after injection of 12 nmoles. Linear dose-response relationships were observed at both times after injection in both ROIs (all P < 0.01). Spin-labeling MRI assessment revealed that parenchymal injection of 2-chloroadenosine produces potent, dose-dependent, and sustained vasodilation over large areas of brain. This treatment and imaging paradigm should facilitate investigation of the effect of CBF promotion in models of traumatic and ischemic brain injury. Magn Reson Med 45:924,929, 2001. © 2001 Wiley-Liss, Inc. [source] Histological effects of tazarotene 0·1% cream vs. vehicle on photodamaged skin: a 6-month, multicentre, double-blind, randomized, vehicle-controlled study in patients with photodamaged facial skinBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2004L.A. Machtinger Summary Background, Topical tazarotene has been shown to offer efficacy in ameliorating multiple effects of photodamage. Objectives, To evaluate the histological effects of tazarotene cream on photodamaged skin. Methods, In this multicentre, double-blind, randomized, vehicle-controlled study, 50 patients with photodamaged facial skin (at least mild fine wrinkling and mottled hyperpigmentation, with at least one of these being moderate) were randomized to apply tazarotene 0·1% cream or vehicle cream to their face, once daily for 24 weeks. Results, Blinded assessments showed that tazarotene was less likely than vehicle to be associated with an increase in keratinocytic and melanocytic atypia, and more likely than vehicle to be associated with a reduction in atypia. Between-group comparisons in distribution of change from baseline categories of severity were in favour of tazarotene (P = 0·055 for keratinocytic atypia, P = 0·034 for melanocytic atypia, and P < 0·001 for the number of granular cell layers). Compared with vehicle, tazarotene was associated with an increase in epidermal polarity (P = 0·008) and epidermal thickness (P = 0·012), and a tendency for stratum corneum compaction. Tazarotene was also associated with widened intercellular spaces (reported as epidermal oedema) relative to vehicle (P < 0·001). Conclusions, Treatment of photodamaged skin with tazarotene is associated with an amelioration of keratinocytic and melanocytic atypia, an improvement in epidermal polarity, and an increase in epidermal thickness. [source] Nitroxide tempo, a small molecule, induces apoptosis in prostate carcinoma cells and suppresses tumor growth in athymic miceCANCER, Issue 6 2005Simeng Suy Ph.D. Abstract BACKGROUND In previous studies, nitroxide tempo (2, 2, 6, 6-tetramethyl-piperidine-1-oxyl), a small molecule, induced cell death in cancer cells. The current study examined the antineoplastic properties of tempo in the human hormone-dependent/hormone-independent prostate carcinoma models (LNCaP, DU-145, and PC-3). METHODS The apoptotic effects of tempo were examined by the flow cytometric analysis of cells labeled with fluorescein isothiocyanate-conjugated annexin-V, and by electron microscopy. Enzymatic assays were performed to measure the activities of 2 cysteine proteases, i.e., caspase-9 and caspase-3, in tempo-treated cells. The effects of tempo on cell proliferation and on cell cycle distribution profiles were measured by the flow cytometric assay using immunofluorescent staining of incorporated 5'-bromo-2'-deoxyuridine (BrdU) coupled with 7-amino-actinomycin D (7-AAD) staining of total DNA. The number of proliferating cells was also determined independently by enzyme-linked immunosorbent assay using chemiluminescent detection of incorporated BrdU. Subcutaneous growth of human prostate carcinoma in athymic mice was monitored after intratumoral administration of tempo into tumor-bearing mice. In addition, cell viability assays were performed to compare the cytotoxic effect of a combination of doxorubicin or mitoxantrone and tempo with single agents. RESULTS Tempo treatment of prostate carcinoma cells caused a significant increase in the number of apoptotic cells compared with control groups (tempo, 2.5 mM, 24 hours: DU-145, approximately 3.4-fold; PC-3, approximately 6,7-fold; tempo 1 mM, 24 hours: LNCaP, approximately 12-fold). Tempo-induced loss of cell viability was blocked partially or completely after pretreatment of cells with actinomycin-D or cycloheximide, suggesting a de novo macromolecule synthesis-dependent mechanism of cell death. Electron microscopy revealed aggregation and marginalization of chromatin in the nuclei of a large number of tempo-treated LNCaP cells. Tempo treatment of LNCaP cells resulted in enhanced activities of caspase-9 (tempo, 5 mM, 15 hours: approximately 2-fold) and caspase-3 (tempo, 2.5 mM, 24 hours: approximately 12-fold). Tempo treatment also led to an enhanced number of cells in G2/M phase of the cell cycle (tempo, 5.0 mM, 24 hours: DU-145, approximately 1.6-fold; PC-3, approximately 1.5-fold; LNCaP, approximately 5.3-fold), and decreased BrdU incorporation indicative of a decline in the number of proliferating cells (tempo, 2.5 mM, 24 or 48 hours; DU-145, approximately 2,3-fold; PC-3, approximately 1.2-fold; LNCaP, approximately 5,10-fold). Administration of tempo into LNCaP tumor-bearing mice resulted in a significant inhibition of tumor growth (percent initial tumor volume [Day 30, n = 4]: vehicle, 845.35 ± 272.83; tempo, 9.72 ± 9.72; tempo vs. vehicle, P < 0.02). In hormone-refractory prostate carcinoma cells, a combination of relatively low doses of tempo and doxorubicin or mitoxantrone caused enhanced cytotoxicity as compared with single agents. CONCLUSIONS These data demonstrated that nitroxide tempo induced apoptosis and activated a caspase-mediated signaling pathway in prostate carcinoma cells. Tempo treatment also caused cell cycle arrest in G2/M phase and decreased the number of proliferating cells (S phase). Tempo treatment of tumor-bearing mice led to inhibition of tumor growth, suggesting that tempo is a novel member of the small-molecule family of antineoplastic agents. Cancer 2005. © 2005 American Cancer Society. [source] Toddlers can adaptively change how they categorize: same objects, same session, two different categorical distinctionsDEVELOPMENTAL SCIENCE, Issue 1 2009Jessica S. Horst Two experiments demonstrate that 14- to 18-month-old toddlers can adaptively change how they categorize a set of objects within a single session, and that this ability is related to vocabulary size. In both experiments, toddlers were presented with a sequential touching task with objects that could be categorized either according to some perceptually salient dimension corresponding to a taxonomic distinction (e.g. animals vs. vehicles) or to some less obvious dimension (e.g. rigid vs. deformable). In each experiment, children with larger productive vocabularies responded to both dimensions, showing evidence of sensitivity to each way of categorizing the items. Children with smaller productive vocabularies attended only to the taxonomically related categorical grouping. These experiments confirm that toddlers can adaptively shift the basis of their categorization and highlight the dynamic interaction between the child and the current task in early categorization. [source] | ||||||||||